Genetic Variant LBP:p.Ala92Ala (chr20-38350847-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004139.5(LBP):c.276G>A(p.Ala92Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,613,664 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

LBP
NM_004139.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.44

Variant links:

Genes affected

LBP (HGNC:6517): (lipopolysaccharide binding protein) The protein encoded by this gene is involved in the acute-phase immunologic response to gram-negative bacterial infections. Gram-negative bacteria contain a glycolipid, lipopolysaccharide (LPS), on their outer cell wall. Together with bactericidal permeability-increasing protein (BPI), the encoded protein binds LPS and interacts with the CD14 receptor, probably playing a role in regulating LPS-dependent monocyte responses. Studies in mice suggest that the encoded protein is necessary for the rapid acute-phase response to LPS but not for the clearance of LPS from circulation. This protein is part of a family of structurally and functionally related proteins, including BPI, plasma cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). [provided by RefSeq, Apr 2012]

LBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 20-38350847-G-A is Benign according to our data. Variant chr20-38350847-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 735262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.44 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBP	NM_004139.5 link	c.276G>A	p.Ala92Ala	synonymous_variant	Exon 3 of 15	ENST00000217407.3	NP_004130.2	P18428Q8TCF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3 link	c.276G>A	p.Ala92Ala	synonymous_variant	Exon 3 of 15	1	NM_004139.5	ENSP00000217407.2		P18428

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

156

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00107

AC:

268

AN:

251022

Hom.:

AF XY:

0.00114

AC XY:

155

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00180

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00142

AC:

2081

AN:

1461342

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

998

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00169

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00102

AC:

156

AN:

152322

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00146

Hom.:

Bravo

AF:

0.00107

EpiCase

AF:

0.00245

EpiControl

AF:

0.00296

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.62

DANN

Benign

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over